Pronounced early increase in circulating leptin predicts a lower weight gain during clozapine treatment.

Weight gain is a widely reported side effect of clozapine, but no predictive factor has been identified so far. We investigated whether pretreatment values of circulating leptin or its early changes during clozapine administration could predict the long-term weight gain induced by the drug. Body weight and plasma levels of leptin were prospectively measured in 22 patients (13 men and 9 women) with drug-resistant schizophrenia undergoing a long-term treatment with clozapine. At the end of the second week of clozapine administration, circulating leptin increased much more than weight gain, and this increase was inversely correlated to body weight increase observed after 6 and 8 months of treatment. These findings suggest that early changes in leptin secretion may predict long-term weight gain in the course of clozapine administration.